We here propose a Specialized Program of Research Excellence in Breast Cancer to meet the needs of the oncologic community for an integrated clinical and laboratory effort dedicated to reducing the incidence of and mortality from breast cancer. The SPORE will be composed of one Director one Scientific Coordinator, a Steering Committee, five main research projects, two core resources (Administrative and Pathology), a Developmental Research Program, and a Career Development Program. The projects will include studies of erbB-2, erbB-3, and erbB-4, heregulin, EGFR, ras and farnesyl protein transferase inhibitors, TC- 21, TGF-beta, representational difference analysis, susceptibility genes (BRCA1), cyclins, and p53. These laboratory investigations will translate into a better understanding of etiology, diagnosis, staging, prognosis, therapeutic response, and quality-of-life. The Steering Committee will consist of the Director (Dr. Norton), the Scientific Coordinator (Dr. N. Rosen), the Head of the Breast Pathology Core Resource (Dr. P. P. Rosen), the leaders of the five main projects (Drs. Aaronson, Massague, Mendelsohn, N. Rosen, Wigler), Dr. Lucio Luzzatto (Human Genetics), Dr. Begg (Biostatistics), Dr. Lloyd Old (Immunology), Dr. Borgen (Surgery), Dr. Beryl McCormick (Radiation Therapy), and Ms. Amy Langer (Executive Director, National Alliance of Breast Cancer Organizations). To expedite an improved SPORE network, we advocate and will organize frequent meetings of the Directors of the funded SPOREs. We would also propose to coordinate our activities with those of representatives of the various NCI- sponsored tissue resource banks/registries other than the SPOREs, and with the chairs of the Cooperative Group Breast Cancer Committees. We have designed an extensive tissue resource to be of value to our SPORE and to the wider network that -we plan to organize. Oversight will be by MSKCC committees and by an eminent Board of Scientific Advisors.